Experimental Retinal Detachment and Reattachment

描述（由申请方提供）：神经视网膜与视网膜色素上皮细胞脱离是视力丧失的严重原因。视网膜在重新附着后具有显著的恢复能力，尽管当涉及黄斑时，视觉恢复通常不是最佳的。在这个项目的过程中，我们发现脱离引发了整个视网膜的一系列复杂的生化和结构变化，包括神经元和神经胶质的显著重塑。我们还发现，再附着引发了其自身的一系列变化，而不仅仅是外节恢复，包括视杆神经突发芽和Muller细胞在视网膜玻璃体表面上的生长。我们还发现，简单地呼吸富氧空气可以减轻许多与脱离相关的退行性变化。我们越了解这些复杂的细胞反应，并最终了解它们背后的分子机制，我们就越有能力开发新的治疗方法来治疗这种和其他视网膜变性。本课题的具体目标是：1）研究视网膜脱离和再附着过程中神经元和神经胶质细胞的重塑以及这种重塑对视网膜回路的影响。2)目的：验证视网膜脱离诱导的视网膜内增殖反应产生多能祖细胞群的假设，并确定增殖细胞的命运。3)为了检验抑制这种反应将减少视网膜下和/或视网膜前膜（PVR）的产生并改变由脱离诱导的变性过程的假设。4)为了验证高氧会改善视网膜复位的细胞结果的假设。5)建立脱离的小鼠模型，并研究两种中间丝蛋白GFAP和波形蛋白缺陷的小鼠，以确定它们在胶质细胞对脱离的反应中的作用。

DESCRIPTION (provided by applicant): Detachment of the neural retina from the retinal pigmented epithelium is a serious cause of visual loss. The retina has a remarkable ability to recover upon reattachment, although visual recovery, when the macula is involved, is often less than optimal. We have discovered over the course of this project that detachment initiates a complex series of biochemical and structural changes throughout the retina, including significant remodeling of both neurons and glia. We have also discovered that reattachment initiates its own set of changes beyond outer segment recovery, including rod neurite sprouting and the growth of Muller cells onto the vitreal surface of the retina. We have also discovered that the simple breathing of oxygen-enriched air can mitigate many of the degenerative changes associated with detachment. The better we understand these complex cellular responses and eventually the molecular mechanism underlying them, the better our position to developing new therapeutic approaches to this and other retinal degenerations becomes. The specific aims for this project are: 1) To study neuronal and glial remodeling in short and long-term detachments and reattachments and the effect of this remodeling on retinal circuitry. 2) To test the hypothesis that the intraretinal proliferative response induced by detachment produces a population of multipotent progenitor cells, and to determine the fate of the proliferating ceils. 3) To test the hypothesis that inhibiting this response will reduce the production of subretinal and/or epiretinal membranes (PVR) and alter the course of degeneration induced by detachment. 4) To test the hypothesis that hyperoxia will improve the cellular outcome of retinal reattachment. 5) To develop a mouse model of detachment and to study mice deficient in the two intermediate filament proteins, GFAP and vimentin to determine their roles in glial cell responsiveness to detachment.